Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice

Nociception is an important type of perception that has major influence on daily human life. There are some descending pathways related to pain management and modulation, which are collectively known as the descending antinociceptive system (DAS). Noradrenalin (NA) in the locus coeruleus (LC) and se...

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Main Authors: Shunpei Moriya, Akira Yamashita, Ryusei Nishi, Yoko Ikoma, Akihiro Yamanaka, Tomoyuki Kuwaki
Format: Article
Language:English
Published: Elsevier 2019-12-01
Series:IBRO Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2451830118300797
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author Shunpei Moriya
Akira Yamashita
Ryusei Nishi
Yoko Ikoma
Akihiro Yamanaka
Tomoyuki Kuwaki
author_facet Shunpei Moriya
Akira Yamashita
Ryusei Nishi
Yoko Ikoma
Akihiro Yamanaka
Tomoyuki Kuwaki
author_sort Shunpei Moriya
collection DOAJ
description Nociception is an important type of perception that has major influence on daily human life. There are some descending pathways related to pain management and modulation, which are collectively known as the descending antinociceptive system (DAS). Noradrenalin (NA) in the locus coeruleus (LC) and serotonin (5-HT) in the rostral ventromedial medulla (RVM) are components of the DAS. Most 5-HT neurons in the dorsal raphe (DR) have ascending projections rather than descending projections, and they project to the thalamus that modulates nociception. Both the DAS and the DR are believed to be involved in pain-emotion symptoms. In this study, we utilized a fiber photometry system to specifically examine the activity of LC NA neurons and RVM/DR 5-HT neurons using mice carrying tetracycline-controlled transactivator transgene (tTA) under the control of either a dopamine β-hydroxylase promoter or a tryptophan hydroxylase-2 promoter and site-specific infection of an adeno-associated virus carrying a TetO G-CaMP6 gene. After confirmation of specific expression of G-CaMP6 in the target populations, changes in green fluorescent signal intensity were recorded in awake mice upon exposure to acute nociceptive stimulation consisting of a pinch and application of heat (55 °C) to the tail. Both stimuli resulted in rapid and transient (<15 s) increases in the activity of LC NA neurons and RVM/DR 5-HT neurons while the control stimuli did not induce any changes. The present results clearly indicate that acute nociceptive stimuli increase the activity of LC NA neurons and RVM/DR 5 H T neurons and suggest a possible therapeutic target for pain treatment. Keywords: G-CaMP6, Fiber photometry, Locus coeruleus (LC), Rostral ventromedial medulla (RVM), Dorsal raphe (DR)
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spelling doaj.art-25815af027ad4191bb63daf92adafe642022-12-22T01:17:59ZengElsevierIBRO Reports2451-83012019-12-01719Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake miceShunpei Moriya0Akira Yamashita1Ryusei Nishi2Yoko Ikoma3Akihiro Yamanaka4Tomoyuki Kuwaki5Department of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, JapanDepartment of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, JapanDepartment of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, JapanDepartment of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, JapanResearch Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, JapanDepartment of Physiology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, Japan; Corresponding author.Nociception is an important type of perception that has major influence on daily human life. There are some descending pathways related to pain management and modulation, which are collectively known as the descending antinociceptive system (DAS). Noradrenalin (NA) in the locus coeruleus (LC) and serotonin (5-HT) in the rostral ventromedial medulla (RVM) are components of the DAS. Most 5-HT neurons in the dorsal raphe (DR) have ascending projections rather than descending projections, and they project to the thalamus that modulates nociception. Both the DAS and the DR are believed to be involved in pain-emotion symptoms. In this study, we utilized a fiber photometry system to specifically examine the activity of LC NA neurons and RVM/DR 5-HT neurons using mice carrying tetracycline-controlled transactivator transgene (tTA) under the control of either a dopamine β-hydroxylase promoter or a tryptophan hydroxylase-2 promoter and site-specific infection of an adeno-associated virus carrying a TetO G-CaMP6 gene. After confirmation of specific expression of G-CaMP6 in the target populations, changes in green fluorescent signal intensity were recorded in awake mice upon exposure to acute nociceptive stimulation consisting of a pinch and application of heat (55 °C) to the tail. Both stimuli resulted in rapid and transient (<15 s) increases in the activity of LC NA neurons and RVM/DR 5-HT neurons while the control stimuli did not induce any changes. The present results clearly indicate that acute nociceptive stimuli increase the activity of LC NA neurons and RVM/DR 5 H T neurons and suggest a possible therapeutic target for pain treatment. Keywords: G-CaMP6, Fiber photometry, Locus coeruleus (LC), Rostral ventromedial medulla (RVM), Dorsal raphe (DR)http://www.sciencedirect.com/science/article/pii/S2451830118300797
spellingShingle Shunpei Moriya
Akira Yamashita
Ryusei Nishi
Yoko Ikoma
Akihiro Yamanaka
Tomoyuki Kuwaki
Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
IBRO Reports
title Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
title_full Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
title_fullStr Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
title_full_unstemmed Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
title_short Acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
title_sort acute nociceptive stimuli rapidly induce the activity of serotonin and noradrenalin neurons in the brain stem of awake mice
url http://www.sciencedirect.com/science/article/pii/S2451830118300797
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